The proposal describes a series of experiments designed to elucidate the rules of mitochondrial transmission genetics and the mechanisms which underly those rules, using a combination of methods at the cellular and molecular levels. Yeast mitochondria will serve as a model system for investigation of general questions concerning the interaction of multiple genomes within a cell, the behavior of organelles during asexual and sexual reproduction, and mechanisms of mutation and recombination. These studies will provide background information for future studies concerning the role of the mitochondrial genome in the development and evolution of organisms. Experiments will use petite and antibiotic-resistant mutations in Saccharomyces cerevisiae. Ethidium bromide-induced metastable states, discovered in previous work on petite mutagenesis, will be further characterized in order to obtain information about the structure and behavior of mitochondrial DNA. Experiments are also proposed which will probe mechanisms involved at each stage of a cross between two haploid cells with different mitochondrial genotypes and the subsequent recombination and segregation of mitochondrial genomes to produce various output ratios of pure-breeding diploids. Experiments will be concerned with the mechanism of mitochondrial interactions in the zygote (complete fusion vs. injection of mitochondrial DNA); whether recombination of mitochondrial DNA is reciprocal; and the roles of selective replication, selective destruction, and selective transmission of mitochondrial DNA in the phenomenon of mitochondrial polarity ("sexuality"). Some experiments will deal specifically with the related problem of suppressiveness in petite mutants (differential replication vs. recombination hypotheses).